Insulin resistance (IR) develops as a response to long term elevation of insulin levels or hyperinsulinemia (HI) after exposure to chronic increases in blood sugar levels. Additionally, IR in conjunction with fatty liver (NAFLD) and an increase in ectopic adipose storage including visceral adiposity tissue (VAT), are shown to increase the risk and further the progression of dyslipidemia, type 2 diabetes (T2D), obesity and cardiovascular disease (CVD).
Recently, studies have indicated that elevations of fat in the liver found in NAFLD are more strongly associated with IR than increased VAT as had been previously thought. This is important, particularly as the incidence of NAFLD has more than doubled in adolescents and adults in the past two decades with current estimates as high as 50% or an estimated 7 million children in the United States. NAFLD is now the most common cause of chronic liver disease in the pediatric population and its diagnosis frequently indicates the presence of prediabetes or T2D. , ,  This fact was supported in a recent survey of 675 children with NAFLD of whom 30% were also found to be prediabetic or to have T2D. 
Excess sugar intake, particularly fructose, is thought to be one of the driving forces behind these alarming statistics. Fructose is converted to fat in the liver in a process called de novo lipogenesis (DNL). The higher the consumption of fructose, the greater the risk for NAFLD. Because fructose comes into the body through diet, it is thought that reducing fructose intake may be one modifiable pathway to reduce NAFLD rates and subsequently lower risk of downstream metabolic dysfunction.
Although fructose is often thought of as a “fruit sugar” it is more commonly consumed in heavily processed forms such as high fructose corn syrup found in sodas, sweetened grain based foods, candy, and other processed “junk” foods. The high consumption of these foods in children is rampant and thus targeting nutritional modifications in children may lead to a shift in reducing their fructose intake; subsequently their risk for NAFLD and future complications including T2D and CVD. This premise was supported by results from a 2017 study that hypothesized short-term restrictions of fructose in children with metabolic syndrome and obesity and who typically consumed high levels of fructose would lead to a reduction in DNL and liver fat.
This study recruited non-diabetic African American and Latino children with obesity and metabolic syndrome who identified as high habitual sugar consumers. Children had to be between 8-18 years of age, have a body mass index z-score greater or equal to 1.8 and have at least one of the following:
- systolic blood pressure >95th percentile for age and sex
- fasting triglycerides >150 mg/dL
- fasting glucose 100 -125 mg/dL and fasting insulin >15 mIU/mL
Initial assessments were conducted on Day 0 and final assessments on Day 10. In the 9 days between, participants were given food to be consumed at home which consisted of pre-made meals restricting sugar and fructose content, resulting in a reduction from their typical diet in total sugar content from 28% to 10% and fructose from 12% to 4% of total energy intake.
Results from this study showed improvements in blood sugar levels, fasting lipoproteins, blood pressure and several other clinical parameters. Moreover, liver fat decreased from a median of 7.2% to 3.8%; VAT decreased from 123 cm3 to 110 cm3. DNL area under the curve also saw an improvement decreasing from 68% to 26%. These improvement occurred irrespective of baseline liver fat. The authors of this study concluded that short-term (9 days) isocaloric fructose restriction decreased liver fat, VAT, and DNL, and improved insulin kinetics in children with obesity indicating a continued need to reduce sugar consumption in youth.
Why is this Clinically Relevant?
- Rates of NAFLD in children and adolescents may be as high as 50% leading to an increased risk of metabolic dysregulation
- High rates of fructose consumption is a leading risk factor for NAFLD
- Reducing fructose consumption is an easy-to-implement, low cost method to decrease liver fat levels, VAT and DNL in children and adolescents and reduce future risk of prediabetes, T2D and cardiovascular disease
- Healthcare providers should routinely ask about children’s diets during office visits particularly focusing on the quantity of fructose containing foods that are being consumed daily
- Educating children and parents on sources of unhealthy fructose is a first good step in beginning the nutrition discussion for families while offering healthier substitutions to support the transition
 Schwimmer JB, Deutsch R, Kahen T, Lavine JE, Stanley C, Behling C. Prevalence of fatty liver in children and adolescents. Pediatrics. 2006;118(4):1388-1393.
 Schwimmer JB, Pardee PE, Lavine JE, Blumkin AK, Cook S. Cardiovascular risk factors and the metabolic syndrome in pediatric nonalcoholic fatty liver disease. Circulation. 2008;118(3):277-283.
 Schwarz JM, et al. Effects of Dietary Fructose Restriction on Liver Fat, De Novo Lipogenesis, and Insulin Kinetics in Children with Obesity. Gastroenterology. 2017;153:743–752.
 Newton KP, Hou J, Crimmins NA, et al. Prevalence of prediabetes and type 2 diabetes in children with nonalcoholic fatty liver disease. JAMA Pediatr 2016; 170(10):e161971.